Different initiation of pre-TCR and γδTCR signalling

Lineage choice is of great interest in developmental biology. In the immune system, the alpha beta and gamma delta lineages of T lymphocytes diverge during the course of the beta-, gamma- and delta-chain rearrangement of T-cell receptor (TCR) genes that takes place within the same precursor cell and which results in the formation of the gamma delta TCR or pre-TCR proteins(1-3). The pre-TCR consists of the TCR beta chain covalently linked to the pre-TCR alpha protein, which is present in immature but not in mature T cells which instead express the TCR alpha chain(4,5). Animals deficient in pre-TCR alpha have few alpha beta lineage cells but an increased number of gamma delta T cells. These gamma delta T cells exhibit more extensive TCR beta rearrangement than gamma delta T cells from wild-type mice(6,7). These observations are consistent with the idea that different signals emanating from the gamma delta TCR and pre-TCR instruct lineage commitment(8). Here we show, by using confocal microscopy and biochemistry to analyse the initiation of signalling, that the pre-TCR but not the gamma delta TCR colocalizes with the p56(lck) Src kinase into glycolipid-enriched membrane domains (rafts) apparently without any need for ligation. This results in the phosphorylation of CD3 epsilon and Zap-70 signal transducing molecules. The results indicate clear differences between pre-TCR and gamma delta TCR signalling.